Fecal Cholesterol Research Articles

Soybean-Derived Peptides Attenuate Hyperlipidemia by Regulating Trans-Intestinal Cholesterol Excretion and Bile Acid Synthesis.

Increased triglyceride, cholesterol, and low-density lipoprotein (LDL) levels cause hyperlipidemia. Despite the availability of statin-based drugs to reduce LDL levels, additional effective treatments for reducing blood lipid concentrations are required. Herein, soybean hydrolysate prepared via peptic and tryptic hydrolysis promoted trans-intestinal cholesterol excretion (TICE) by increasing ATP-binding cassette subfamily G member 5 (ABCG5) and ABCG8 expression. The peptide sequence capable of promoting TICE was determined via HPLC and LC-MS/MS. Based on this, pure artificial peptides were synthesized, and the efficacy of the selected peptides was verified using cellular and hyperlipidemic mouse models. Soybean hydrolysates, including two bioactive peptides (ALEPDHRVESEGGL and SLVNNDDRDSYRLQSGDAL), promoted TICE via the expression of ABCG5 and ABCG8 in enterocytes. They downregulated expression of hepatic cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1 via expression of fibroblast growth factor 19 (FGF19) in a liver X receptor α (LXRa)-dependent pathway. Administration of bioactive peptides to hyperlipidemic mouse models by oral gavage reduced cholesterol levels in serum via upregulation of ABCG5 and ABCG8 expression in the proximal intestine and through fecal cholesterol excretion, upregulated FGF 15/19 expression, and suppressed hepatic bile acid synthesis. Oral administration of soybean-derived bioactive peptides elicited hypolipidemic effects by increasing TICE and decreasing hepatic cholesterol synthesis.

Inhibitory Effect of Lactobacillus plantarum KFY02 Fermented Lemon Juice on Obesity and Intestinal Regulation in Mice Fed with High-fat Diet

The purpose of this study was to observe the fat reducing effect of lemon juice fermented by Lactobacillus plantarum KFY02 and its regulation on intestinal flora. This study induced obesity in mice through the establishment of high-fat diet, the experimental mice were divided into normal group, model group, Lactobacillus plantarum KFY02 group, unfermented lemon juice group and fermented lemon juice group, and biochemical kits, section observation and quantitative PCR were used to detect the related indexes of mouse serum and tissue, and the composition of intestinal microorganisms was observed by detecting the expression of microorganisms in feces. The results showed that Lactobacillus plantarum KFY02, unfermented lemon juice and fermented lemon juice could effectively reduce the body weight of obese mice, reduce the organ index of liver and epididymal adipose tissue in obese mice, and reduce the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and raise high density lipoprotein cholesterol (HDL-C) in serum and liver tissue of obese mice, and also could increase the contents of total cholesterol (TC), triglyceride (TG) and total protein (TP) in mouse feces. H&E pathological observation showed that Lactobacillus plantarum KFY02, unfermented lemon juice and fermented lemon juice could also reduce liver tissue lesions and adipocyte enlargement and accumulation caused by obesity. qPCR results showed that Lactobacillus plantarum KFY02, unfermented lemon juice and fermented lemon juice could up-regulate PPAR-α, CPT-1, LPL, CYP7A1 and down-regulate C/EBPα, PPAR-γ mRNA expression in liver tissue of obese mice induced by high fat diet, meanwhile, they could also up-regulate the expression of Bacteroidetes, Lactobacillus sp., Bifidobacterium sp. and down-regulate the expression of Firmicutes. These results showed that Lactobacillus plantarum KFY02, unfermented lemon juice and fermented lemon juice could reduce fat in mice, and the effect of fermented lemon juice was the best. The fat reduction effect of fermented lemon juice on mice was directly related to its regulation of intestinal function and microbial composition. It could be seen that lemon juice fermented by Lactobacillus plantarum KFY02 had good lipid-lowering and intestinal regulation in obese mice.

Effect of Monoclonal Antibody Blockade of Long Fragment Neurotensin on Weight Loss, Behavior, and Metabolic Traits After High-Fat Diet Induced Obesity.

BackgroundObesity is a major public health problem of our time as a risk factor for cardiometabolic disease and the available pharmacological tools needed to tackle the obesity pandemic are insufficient. Neurotensin (NTS) is a 13 amino acid peptide, which is derived from a larger precursor hormone called proneurotensin or Long Form NTS (LF NTS). NTS modulates neuro-transmitter release in the central system nervous, and facilitates intestinal fat absorption in the gastrointestinal tract. Mice lacking LF NTS are protected from high fat diet (HFD) induced obesity, hepatic steatosis and glucose intolerance. In humans, increased levels of LF NTS strongly and independently predict the development of obesity, diabetes mellitus, cardiovascular disease and mortality. With the perspective to develop therapeutic tools to neutralize LF NTS, we developed a monoclonal antibody, specifically inhibiting the function of the LF NTS (LF NTS mAb). This antibody was tested for the effects on body weight, metabolic parameters and behavior in mice made obese by high-fat diet.MethodsC57bl/6j mice were subjected to high-fat diet (HFD) until they reached an obesity state, then food was switched to chow. Mice were treated with either PBS (control therapy) or LF NTS mAb at the dose of 5 mg/kg once a week (i.v.). Mice weight, plasma biochemical analysis, fat and muscle size and distribution and behavioral tests were performed during the losing weight period and the stabilization period.ResultsObese mice treated with the LF NTS mAb lost weight significantly faster than the control treated group. LF NTS mAb treatment also resulted in smaller fat depots, increased fecal cholesterol excretion, reduced liver fat and larger muscle fiber size. Moreover, mice on active therapy were also less stressed, more curious and more active, providing a possible explanation to their weight loss.ConclusionOur results demonstrate that in mice subjected to HFD-induced obesity, a blockade of LF NTS with a monoclonal antibody results in reduced body weight, adipocyte volume and increased muscle fiber size, possibly explained by beneficial effects on behavior. The underlying mechanisms as well as any future role of LF NTS mAb as an anti-obesity agent warrants further studies.

Chronic Oral Administration of Mineral Oil Compared With Corn Oil: Effects on Gut Permeability and Plasma Inflammatory and Lipid Biomarkers.

We investigated the effects of chronic oral administration of mineral oil, versus corn oil as control, on intestinal permeability, inflammatory markers, and plasma lipids in APOE*3-Leiden.CETP mice. Mice received mineral oil or corn oil 15 or 30 μL/mouse/day for 16 weeks (15 mice/group). Intestinal permeability was increased with mineral versus corn oil 30 µL/day, shown by increased mean plasma FITC-dextran concentrations 2 h post-administration (11 weeks: 1.5 versus 1.1 μg/ml, p = 0.02; 15 weeks: 1.7 versus 1.3 μg/ml, p = 0.08). Mean plasma lipopolysaccharide-binding protein levels were raised with mineral versus corn oil 30 µL/day (12 weeks: 5.8 versus 4.4 μg/ml, p = 0.03; 16 weeks: 5.8 versus 4.5 μg/ml, p = 0.09), indicating increased intestinal bacterial endotoxin absorption and potential pro-inflammatory effects. Plasma cholesterol and triglyceride concentrations were decreased with mineral oil, without affecting liver lipids among treated groups. Fecal neutral sterol measurements indicated increased fecal cholesterol excretion with mineral oil 30 µL/day (+16%; p = 0.04). Chronic oral administration of mineral oil in APOE*3-Leiden.CETP mice increased intestinal permeability, with potential pro-inflammatory effects, and decreased plasma cholesterol and triglyceride levels. Our findings may raise concerns about the use of mineral oil as a placebo in clinical studies.

Aflatoxin B1 Induces Gut-Inflammation-Associated Fecal Lipidome Changes in F344 Rats

Abstract Aflatoxin B1 (AFB1) induced intestinal epithelial damage in rodent models, which indicates that long-term exposure to AFB1 may cause chronic gut disorders. In this study, we tested the hypothesis that AFB1-induced adverse effects on gut is mediated by gut-microbiota, which is partially reflected by the changes of fecal microbiome and metabolome. F344 rats were orally exposed to AFB1 of 0, 5, 25, and 75 µg kg−1 body weight for 4 weeks and fecal samples were collected. An ion-fragmentation-spectrum-based metabolomics approach was developed to investigate the fecal microbiota-associated metabolic changes in fecal samples. We found that AFB1 inhibited the hepatic and intestinal metabolism of bile constituents. As compared with the controls, bile acid synthesis-associated cholesterols in rats treated with 25 µg kg−1 (the middle-dose group) were significantly decreased in the fecal samples, for example, lathosterol (45% reduction), cholesterol ester (21% reduction), chenodeoxycholic acid (20% reduction), dihydroxycholesterol (55% reduction), hydroxycholesterol (20% reduction), and 5-cholestene (29% reduction). Although disease-associated lipids were not detectable in the feces of the control group, they were found in AFB1-treated groups, including diglyceride, monoacylglyceride, 19,20-dihydroxy-docosapentaenoic acid, and phosphatidylethanolamine. Metabolisms of carbohydrates and production of short-chain fatty acids were remarkedly decreased in all treated groups. Moreover, an inflammatory-bowel-disease (IBD)-associated taxonomic structure of fecal microbiota was observed as ∼25% Lachnospiraceae, ∼25% Ruminococcaceae, and <1% Lactobacillales, which was similar to the composition pattern found in IBD patients. These results suggest that AFB1-induced disruption on gut-microbiota, partially reflected by fecal microbiome and metabolome, may play important roles in the pathogenesis of chronic gut disorders.

Safety assessment of two strains and anti-obese effects on mice fed a high-cholesterol diet

Previous study documented that Lactobacillus paracasei S0940 and Streptococcus thermophilus ldbm1 have obvious cholesterol-lowering abilities in vitro. In this study, the safety of two strains were evaluated by nitroreductase test, hemolysis test and antibiotic sensitivity test and to evaluate the cholesterol-reducing abilities in vivo. The results indicated that two strains did not exhibit nitroreductase activities and were ɤ-hemolytic on blood agar plates. Further, both strains did not represent a health risk by antibiotic sensitivity test, and significantly reduced serum and liver cholesterol and triglyceride levels of high fat-fed mice. Compared with the high-fat model group, administration of the strains to mice fed a high-cholesterol diet increased fecal water content and fecal cholesterol and significantly improved the intestinal microbiota, which indicating that Lactobacillus paracasei S0940 and Streptococcus thermophilus ldbm1 have a positive effect on reducing cholesterol levels and may be used in functional food.

Regulation of the expression of cholesterol transporters by lipid-lowering drugs ezetimibe and pemafibrate in rat liver and intestine

Ezetimibe and pemafibrate are lipid-lowering drugs and promote reverse cholesterol transport. However, it is unknown whether cholesterol is mainly excreted by hepatobiliary excretion or by non-biliary transintestinal cholesterol efflux (TICE). We evaluated the effects of ezetimibe and pemafibrate on hepatic and intestinal cholesterol transporter regulation in Sham-operated rats, and examined the effects of these drugs on TICE in bile duct-ligated rats. Seven-week-old male Sprague-Dawley rats were treated as follows for two weeks: 1) Sham, Sham operation; 2) BDL, bile duct ligation; 3) E-Sham, Sham + ezetimibe; 4) E-BDL, BDL + ezetimibe; 5) P-Sham, Sham + pemafibrate; and 6) P-BDL, BDL + pemafibrate. Blood, liver, jejunum, and feces were collected 72 h post-surgery. Hepatic cholesterol levels were decreased in P-Sham and E-Sham, and were lower in E-BDL and P-BDL than in BDL. Fecal cholesterol levels increased in E-Sham and P-Sham compared with Sham, and were higher in E-BDL and P-BDL than in BDL. In liver, Abcg5 mRNA showed induction in E-Sham, Abcg5 and Abca1 mRNA were induced in P-Sham, Abcg5 mRNA was reduced in E-BDL, and Abca1 mRNA was increased in P-BDL. In jejunum, Abcg5 mRNA was induced in E-Sham. Abcg8 mRNA was induced in E-Sham and P-Sham. NPC1L1 mRNA showed reduced expression in P-Sham and P-BDL. SR-B1 mRNA was reduced in P-Sham, and the expression decreased in P-BDL. LDL receptor mRNA was induced in BDL and P-BDL. Ezetimibe and pemafibrate may promote TICE by increasing Abcg5/g8, while pemafibrate may inhibit intestinal cholesterol absorption by decreasing SR-B1 and NPC1L1.

Ligustrum robustum Alleviates Atherosclerosis by Decreasing Serum TMAO, Modulating Gut Microbiota, and Decreasing Bile Acid and Cholesterol Absorption in Mice.

Atherosclerosis (AS) is closely related to gut microbiota. Previous studies demonstrates that Ligustrum robustum (LR), a flavonoid-rich tea like plant, can mitigate several AS-related risk factors and modulate gut microbiota in animal models and human subjects. But its anti-AS effect and mechanisms remain unclear. Therefore, in this study, impacts of LR on AS development are investigated and the potential underlying mechanisms in C57BL/6J and Apoe-/- mice are explored. Female C57BL/6J and Apoe-/- mice are fed a chow diet or high-choline diet, supplemented with vehicle (water) or LR water extract (700 mg kg-1 ) by gavage for 17 weeks. It is found that LR attenuates diet-induced AS by reducing serum trimethylamine and trimethylamine-N-oxide (TMAO) levels likely by modulating gut microbiota. Moreover, LR increases the abundance of the genus Bifidobacterium, which generates bile salt hydrolase, and thus presumably enhances bile acid (BA) deconjugation and increases fecal BA excretion. Meanwhile, LR increases fecal cholesterol excretion, decreases the levels of serum and hepatic cholesterol, but did not affect short-chain fatty acids in feces. LR attenuates AS development presumably by decreasing serum TMAO levels and increasing fecal BA excretion likely via gut microbial modulation. These effects are accompanied by increases in fecal cholesterol excretion and decreases in serum and hepatic cholesterol.

Metabolomics Profiling Revealed Double-Edged Metabolic Effects of Functionalized Wheat Bran in Mouse

Abstract Objectives Wheat bran is rich in bioactive components, mainly dietary fiber, micronutrients, and phytochemical contents. However, the health-promoting effects of wheat bran is restricted by the high-degree crosslinking of dietary fiber and low bioavailability of phytochemicals. The present study aims to improve the functions of wheat bran by increasing the levels of soluble fiber and free ferulic acid from optimized processing to examine the metabolic effects of consuming functionalized wheat bran (FWB) in mice. Methods Control wheat bran (CWB) was processed by an optimized combination of milling, high pressure pulverization, and alkali treatment, leading to dramatic increases of soluble fiber and free ferulic acid. Three groups of male mice were fed the control AIN93G diet, and two modified AIN93G diets containing 10% of CWB and 10% FWB, respectively, for 7 days. The effects of CWB and FWB on the mouse metabolome were determined through the LC-MS based metabolomics analysis of feces, liver, serum, and urine samples. Results The processing dramatically improved the function-associated physicochemical properties of wheat bran, including the increases of soluble fiber content and viscosity by milling and high-pressure pulverization and the elevation of free ferulic acid by alkali treatment. FWB feeding elevated microbial SCFAs production, promoted the excretion of bile acids and cholesterol in feces, modified the lipidome in the liver, decreased triacylglycerols and cholesterol in serum, and increased the levels of ferulic acid and microbial metabolites in urine. On the other hand, FWB feeding resulted in the increases of free amino acids in feces and the decreases of essential amino acids, choline and its metabolites in the liver. Conclusions The optimized processing dramatically increased the soluble fiber and free ferulic acid contents of wheat bran, resulting in improved hypocholesterolemic and antioxidant functions of FWB. However, the bioavailability of nutrients, including essential amino acids and choline, and the homeostasis of lipidome could be negatively affected by FWB diet. These double-edged metabolic effects warrant further investigations on how to achieve the balance between the functionalization of bioactive components and the disruption of nutrient bioavailability in wheat bran processing. Funding Sources NIFA project MIN-18–125.

High hydrostatic pressure extract of mulberry leaves ameliorates hypercholesterolemia via modulating hepatic microRNA-33 expression and AMPK activity in high cholesterol diet fed rats.

BackgroundMulberry leaf (Morus alba L.) contains multiple bioactive ingredients and has been used in the treatment of obesity, diabetes, inflammation, and atherosclerosis. High hydrostatic pressure (HHP) processing has been developed for the extraction of bioactive compounds from plants. However, the hypocholesterolemic effect of the HHP extract from mulberry leaves and its underlying mechanism have never been investigated.ObjectiveThe specific aim of the present study was to investigate the hypocholesterolemic property of a novel extract obtained from mulberry leaves under HHP in rats.DesignSprague–Dawley rats were divided into four groups and fed either a normal diet (NOR), a high cholesterol diet containing 1% cholesterol and 0.5% cholic acid (HC), an HC diet containing 0.5% mulberry leaf extract (ML), or a 1% mulberry leaf extract (MH) for 4 weeks.ResultsHigh hydrostatic pressure extract of mulberry leaves significantly reduced the HC-increased serum levels of triglyceride (TG), cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and hepatic contents of TG and TC. The HHP extraction from mulberry leaves also increased the HC-decreased fecal TC and bile acid levels without changing body weight, food intake, liver weight, and serum activities of alanine transaminase (ALT) and aspartate transaminase (AST) (P < 0.05). The mulberry leaf extract significantly enhanced the expression of hepatic genes such as cholesterol 7 alpha-hydroxylase (CYP7A1), liver X receptor alpha (LXRα), and ATP-binding cassette transporters, ABCG5/ABCG8, involved in hepatic bile acid synthesis and cholesterol efflux (P < 0.05). In addition, the HHP extraction of mulberry leaves significantly suppressed hepatic microRNA(miR)-33 expression and increased adenosine monophosphate-activated protein kinase (AMPK) activity.ConclusionThese results suggest that the HHP extract of mulberry leaves lowers serum cholesterol levels by partially increasing hepatic bile acid synthesis and fecal cholesterol excretion through the modulation of miR-33 expression and AMPK activation in the liver.

Canagliflozin Facilitates Reverse Cholesterol Transport Through Activation of AMPK/ABC Transporter Pathway.

Background and PurposeCholesterol is an essential lipid and its homeostasis is a major factor for many diseases, such as hyperlipidemia, atherosclerosis, diabetes, and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Cana) is a new kind of hypoglycemic agent, which decreases urinary glucose reabsorption and reduces hyperglycemia. Cana has been shown to regulate serum lipid, decrease serum triglyceride and increase serum high-density lipoprotein-cholesterol (HDL-C), and improve cardiovascular outcomes. But evidence of how Cana impacted the cholesterol metabolism remains elusive.MethodsWe treated Cana on mice with chow diet or western diet and then detected cholesterol metabolism in the liver and intestine. To explore the mechanism, we also treated hepG2 cells and Caco2 cells with different concentrations of Cana.ResultsIn this study, we showed that Cana facilitated hepatic and intestinal cholesterol efflux. Mechanically, Cana via activating adenosine monophosphate-activated protein kinase (AMPK) increased the expression of ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 in liver and intestine, increased biliary and fecal cholesterol excretion.ConclusionThis research confirms that Cana regulates cholesterol efflux and improves blood and hepatic lipid; this may be a partial reason for improving cardiovascular disease.

Dietary Supplementation of Carob and Whey Modulates Gut Morphology, Hemato-Biochemical Indices, and Antioxidant Biomarkers in Rabbits.

This study aimed to evaluate the influence of the carob powder (CP) and sweet whey powder (WhP) inclusion into weaning feed on the gut morphology, hemato-biochemical parameters, and antioxidant biomarkers. The addition of 10 g/kg (basal diet +10 g/kg of CP, of WhP) or the mixture (5 g/kg of CP and 5 g/kg of WhP) in the rabbit's standard diet was assessed. A total of 40 weaned New Zealand White rabbits (4 weeks old) was distributed according to body weight (BW) into four treatments (n = 10) and the feed additives were provided for 7 weeks. Tissue samples and blood were obtained after slaughter. Final BW, daily weight gain, feed conversion ratio, intestinal morphology, and carcass dressing were positively affected by CP-WhP treatments compared with the control diet. Also, CP-WhP treatments significantly increased total proteins, calcium and iron levels, fecal cholesterol excretion, total antioxidants capacity, superoxide dismutase, and catalase in different tissues and significantly decreased total cholesterol, triglycerides, and glucose in blood serum. These changes were associated with a diminution of blood tumor necrosis factor alpha, lipid peroxidation, and carbonyl proteins in rabbit tissues. Both the additives separately and especially in the mix may enhance productive performance, protein profile, gut function, immunity, and antioxidant activity, with reducing lipid peroxidation, essential inflammatory mediator, and protein-carbonyl residues of growing rabbits. These findings suggest that CP-WhP dietary supplementation provides novel insights into a variety of bioactive compound mixtures with different beneficial modes of actions.

Evaluation of Beneficial and Adverse Effects of a Diet Supplemented with Schisandrae Fructus Seed Ethanol Extract on Lipid and Glucose Metabolism in Normal and Hypercholesterolemic/Hyperglycemic Mice.

Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baillon, has been used for the treatment of liver injury and metabolism-related disorders in China. The objective of this study was to investigate the effects of supplementation with ethanol extract of SF seed (EtSF-S) on serum/hepatic lipid and glucose levels as well as fecal total cholesterol (TC) contents in mice fed a normal diet (ND) or high-fat/fructose diet (HFFD) containing 15% lard oil and 15% fructose. Female ICR mice (18–20 g in body weight) were fed with ND or HFFD for 3 months, and then EtSF-S was added to both chow diets at increasing concentrations of 1, 5, and 10% (w/w). Thirty days later, serum and hepatic lipids, including TC, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucose, were measured. Dietary supplementation with EtSF-S reduced hepatic TC (36 and 18%) and TG levels (38 and 28%) and increased serum HDL/LDL ratio (16 and 26%) in both ND- and HFFD-fed mice, respectively. Moreover, supplementation with EtSF-S elevated serum HDL (31%) in HFFD-fed mice and reduced serum LDL (27%) in ND-fed mice. EtSF-S treatment reduced fat mass (40%) in ND-fed mice and increased fecal TC contents (33%) in HFFD-fed mice. EtSF-S supplementation decreased hepatic glucose contents (29%) in both ND- and HFFD-fed mice. However, diet supplemented with EtSF-S elevated serum TG levels (up to 123%) and hepatic size (28%), but more importantly, suppressed the body weight gain (approximately 130%) in mice fed with HFFD. These findings suggested that dietary supplementation with EtSF-S as natural herbal function food may be a useful strategy for the treatment of patients with fatty liver disease or overweight without a high intake of sugar and fat.

Increased Hepatic Lipogenesis Elevates Liver Cholesterol Content.

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoprotein-triglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.

E17241 as a Novel ABCA1 (ATP-Binding Cassette Transporter A1) Upregulator Ameliorates Atherosclerosis in Mice.

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Effectiveness of Chitosan as a Dietary Supplement in Lowering Cholesterol in Murine Models: A Meta-Analysis.

This study presents a meta-analysis of studies that investigate the effectiveness of chitosan administration on lifestyle-related disease in murine models. A total of 34 published studies were used to evaluate the effect of chitosan supplementation. The effect sizes for various items after chitosan administration were evaluated using the standardized mean difference. Using Cochran’s Q test, the heterogeneity of effect sizes was assessed, after which a meta-ANOVA and -regression test was conducted to explain the heterogeneity of effect sizes using the mixed-effect model. Publication bias was performed using Egger’s linear regression test. Among the items evaluated, blood triglyceride and HDL-cholesterol showed the highest heterogeneity, respectively. Other than blood HDL-cholesterol, total cholesterol, and triglyceride in feces, most items evaluated showed a negative effect size with high significance in the fixed- and random-effect model (p < 0.0001). In the meta-ANOVA and -regression test, administering chitosan and resistant starch was revealed to be most effective in lowering body weight. In addition, chitosan supplementation proved to be an effective solution for serum TNF-α inhibition. In conclusion, chitosan has been shown to be somewhat useful in improving symptoms of lifestyle-related disease. Although there are some limitations in the results of this meta-analysis due to the limited number of animal experiments conducted, chitosan administration nevertheless shows promise in reducing the risk of cholesterol related metabolic disorder.

Effect of bile salt hydrolase-active Lactobacillus plantarum Y15 on high cholesterol diet induced hypercholesterolemic mice

ABSTRACT This study aimed to elucidate the underlying mechanisms for the protective effect of Lactobacillus on hypercholesterolemia. Firstly, twenty Lactobacillus strains were screened for potential probiotics with high bile salt hydrolase (BSH) activity using in vitro methods. Secondly, hypercholesterolemic mice induced by a cholesterol-enriched diet were administrated by the probiotic candidate strain L. plantarum Y15, identified from the screen. Results in vitro showed that L. plantarum Y15 possessed high BSH activity. In vivo, L. plantarum Y15 supplementation decreased total cholesterol and triglyceride in serum and liver, increased total cholesterol and total bile acid in feces, and alleviated histopathological changes in the liver. Furthermore, L. plantarum Y15 supplementation modulated the gut microbiota to the control group’s pattern, leading to increase BSH activity, which further influence FXR and SHP signaling pathway to upregulate the expression level of CYP7A1 to enhance the cholesterol catabolism.

Beneficial Effects of Algerian Green Alga Ulva lactuca and Its Hydroethanolic Extract on Insulin Resistance and Cholesterol Reverse Transport in High-Fat/Streptozotocin Diabetic Rats

The aim of this study was to evaluate the impact of the green algae Ulva lactuca and its hydroethanolic extract on insulin resistance and cholesterol reverse transport in type 2 diabetic (T2D) rats. Rats had T2D induced by a high-fat diet (HFD) for 5 weeks followed by intraperitoneal injection of streptozotocin. Diabetic rats were divided into three groups and were fed a HFD in the presence or absence of 1% alga (HFD-Alg) or 1% of its hydroethanolic extract (HFD-Ext), for 4 weeks. The control group consumed 20% casein combined with 5% lipids. Hyperglycemia, insulin resistance, hypercholesterolemia, and hypertriglyceridemia were noted in HFD rats vs control rats. Whole alga and its extract decreased these parameters vs the HFD. Moreover, fecal total cholesterol and triacylglycerols levels were lowered in HFD group vs C group, but were increased with HFD-Alg vs HFD. Compared with the Control, the HFD group had decreased lecithin:cholesterol acyltransferase (LCAT) activity, apolipoprotein A-I (ApoA-I), high-density lipoprotein (HDL3)-phospholipids (PL), and HDL2-cholesteryl ester (CE) levels, but increased HDL3-unesterified cholesterol (UC) levels. Furthermore, compared with the HFD group, the HFD-Alg and HFD-Ext groups had increased LCAT activity, ApoA-I, HDL3-PL, and HDL2-CE levels and decreased HDL3-UC levels. In addition, in the HFD-Ext group, LCAT activity and ApoA-1 levels were decreased vs the HFD-Alg whereas HDL3-UC levels were increased. In conclusion, these results indicate that U. lactuca and its hydroethanolic extract have curative effect on T2D. Therefore, this alga could be considered a functional food supplement for the treatment and prevention of diabetes.

Thymus atlanticus polyphenol-rich extract regulates cholesterol metabolism by inhibiting its biosynthesis without affecting its excretion in hamsters fed a high-fat diet

Context Thymus atlanticus has been reported to have significant hypolipidaemic effect in animal models. However, the mechanism of this hypolipidaemic action still unknown. Objective To determinate the possible mechanism(s) of hypolipidaemic action of a Thymus atlanticus polyphenol-rich extract (PRE). Materials and methods Plasma, faecal, and liver cholesterol, bile acid content in the faeces, and gene expression level of HMG-CoA reductase, CYP7A1, ABCG5 and ABCG8 were analysed after 9 weeks in hamsters feeding normal diet, high-fat diet (HFD) or HFD supplemented with 400 mg/kg body weight/day of PRE. Results PRE significantly decreased total cholesterol content (p < .05) and HMG-CoA reductase expression (p < .05), but did not affect the faecal cholesterol, bile acid contents and CYP7A1 and ABCG5/G8 expression (p > .05). Conclusion We can conclude that the T. atlanticus extract is efficient in the alleviation of chronic hyperlipidaemia by acting as cholesterol biosynthesis inhibitor.

California strawberry consumption increased the abundance of gut microorganisms related to lean body weight, health and longevity in healthy subjects

It was our hypothesis that foods high in polyphenols and fiber have prebiotic activity. This human intervention study aimed to determine if daily consumption of freeze-dried California strawberry powder (SBP) leads to changes in the intestinal microbiota, fecal cholesterol and bile acid (BA) microbial metabolites. Fifteen healthy adults consumed a beige diet+26 g of SBP for 4 weeks, followed by 2 weeks of beige diet only. Stool samples were collected at 0, 4, and 6 weeks. Fecal microbiota was analyzed by 16S rRNA sequencing; fecal cholesterol, BA, and microbial metabolites by gas chromatography. Confirming compliance, urine concentration of pelargonidin, urolithin A glucuronide and dimethylellagic acid glucuronide were present after 4 weeks of SBP consumption. Daily SBP altered the abundance of 24 operational taxonomic units (OTUs). Comparing week 4 to baseline the most significant increases were observed for one OTU from Firmicutes\\Clostridia\\ Christensenellaceae\\NA, one OTU from Firmicutes\\ Clostridia\\Mogibacteriacea\\NA, one OTU from Verrucomicrobia\\ Verrucomicrobiaceae\\Akkermansia\\Muciniphila, one OTU from Actinobacteria\\ Bifidobacteriaceae\\Bifidobacterium\\NA, and one OTU from Bacteroidetes\\Bacteroidia\\ Bacteroidaceae\\Bacteroides and decrease of one OTU from Proteobacteria\\ Betaproteobacteria\\Alcaligenaceae\\Sutterella. Comparing week 4 to 6, we observed a reversal of the same OTUs from C Christensenellaceae, V muciniphilia and C Mogibacteriaceae. Fecal short chain fatty acids and most of the fecal markers including cholesterol, coprostanol, primary and secondary BAs were not changed significantly except for lithocholic acid, which was increased significantly at week 6 compared to baseline. In summary, SBP consumption increased the abundance of gut microorganisms related to lean body weight, health and longevity, and increased fecal lithocholic acid at week 6 in healthy study participants.